This study looked at a pig hormone called nesfatin‑1 (made from the NUCB2 gene) and found it can reduce food intake and boost a reproductive hormone in young female pigs. It also linked a genetic variation in the NUCB2 gene to body weight at puberty, but it does not provide any guidance for using melanotan‑I in humans.

Nesfatin-1, a product of the nucleobindin 2 (NUCB2) gene, purportedly plays important roles in whole-body energy homeostasis. Experiments were conducted to determine how NUCB2 expression in fat depots may be controlled in the pig and to test the hypothesis that nesfatin-1 regulates appetite and LH secretion in the gilt. Prepubertal gilts were used to study expression of NUCB2 in fat and the effects of intracerebroventricular (i.c.v.) injection of nesfatin-1 on food intake and pituitary hormone secretion. Growing pigs (gilts and barrows at 22 wk of age, n = 1,145) or sexually mature gilts (n = 439) were used to test association of SNP in the NUCB2 gene with growth traits. The expression of NUCB2 was similar for subcutaneous fat compared with perirenal fat. An i.c.v. injection of the melanocortin-4 receptor agonist [Nle⁴, d-Phe⁷]-α-melanocyte-stimulating hormone did not alter expression of NUCB2 mRNA in the hypothalamus but reduced (P = 0.056) NUCB2 mRNA expression in subcutaneous fat. Short-term (7 d) submaintenance feeding reduced (P < 0.05) BW and did not alter expression of mRNA for NUCB2, visfatin, or leptin but increased (P < 0.05) expression of adiponectin mRNA in fat. Central injection of nesfatin-1 suppressed (P < 0.001) feed intake. Secretion of LH was greater (P < 0.01) after i.c.v. injection of nesfatin-1 than after saline. Single nucleotide polymorphisms in the porcine NUCB2 gene were not associated with adiposity of growing pigs or age at puberty in gilts but were associated (P < 0.05) with BW at puberty. These data indicate that NUCB2 is expressed in fat depots of the pig and that the level of expression is sensitive to stimulation of appetite-regulating pathways in the hypothalamus. It is confirmed herein that nesfatin-1 can regulate appetite in the pig and affect the gonadotropic axis of the prepubertal pig. Association of SNP in the porcine NUCB2 gene with BW at puberty suggests that regulation of appetite by nesfatin-1 in the pig affects growth, which may have important consequences for adult phenotypes.